Amyotrophic Lateral Sclerosis
Conditions
Keywords
ALS, Stathmin-2, STMN2, ASO, Antisense Oligonucleotide
Brief summary
The primary objective of this study is to determine the safety and tolerability of multiple doses of QRL-201 in people living with ALS
Detailed description
This first-in-human, Phase 1 study will evaluate the safety, tolerability, and pharmacokinetics (PK) of QRL-201 administered intrathecal (IT) to participants with Amyotrophic Lateral Sclerosis. Two dose escalation cohorts of 8 participants each, followed by an additional 48 participants, receiving the study drug in a 6:2 ratio of QRL-201 to placebo.
Interventions
DRUGMultiple ascending doses of QRL-201
Multiple ascending doses of QRL-201 will be intrathecally administered to individuals with sporadic ALS.
Multiple ascending doses of placebo comparator will be intrathecally administered to individuals with sporadic ALS.
DRUGQRL-201
QRL-201 will be intrathecally administered to individuals with C9orf72 ALS.
DRUGPlacebo
Placebo comparator will be intrathecally administered to individuals with C9orf72 ALS.
Sponsors
QurAlis Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Multiple-ascending doses of QRL-201 or placebo will be administered. The dose levels may change subject to available nonclinical, clinical, safety, and PK data.
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
(Double-Blind Periods): * Male or female participants aged 18 to 80 years diagnosed with ALS * ALS symptom onset within 24 months of Screening * Slow vital capacity \>50% * Clinical or electrodiagnostic evidence of lower motor neuron involvement * Not pregnant and not nursing * Willing and able to practice effective contraception * Able to tolerate lumbar puncture * If on approved therapies for the treatment of ALS during the course of the study, must be on a stable dose (at the Sponsor's discretion)
Exclusion criteria
(Double Blind Periods): * Pathogenic variant, likely pathogenic variant, or variant of uncertain significance in the superoxide dismutase 1 (SOD1) and/or fused in sarcoma (FUS) genes * Currently enrolled in any other clinical study involving either an investigational product (IP) or off-label use of a drug or device * Prior exposure to stem cell or gene therapy products * Any contraindication to intrathecal drug administration * Abnormal laboratory values deemed clinically significant by the Investigator * Significant infection or known inflammatory process * Any sign and/or history of neurological conditions and other neuromuscular disorders that could affect the electrophysiological recordings. * An EEG that shows signs of abnormal electrical activity (e.g., epilepsy) Inclusion Criteria (Open-Label Extended Dosing Period): * Male or female participants in the sporadic ALS and C9orf72 ALS Cohorts of QRL-201-01 who have completed through at least Day 253 of safety follow up in the double-blind study period OR have completed Cohort 1 of Cohort 2 * Not pregnant and not nursing * Willing and able to practice effective contraception * Can visit study site for required visits * Able to tolerate lumbar puncture * If on approved therapies for the treatment of ALS during the course of the study, must be on a stable dose (at the Sponsor's discretion)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with one or more treatment emergent adverse events and serious adverse events | Baseline through Day 421 [End of Study Visit | Endpoints: A summary of treatment emergent adverse events, serious adverse events, and other non-serious adverse events, regardless of causality, will be reported in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (plasma): Maximum observed concentration of QRL-201 (Cmax) | Predose up to 24 hours post dose | Endpoints: PK: Cmax of QRL-201 |
| Pharmacokinetics (plasma): Area under the concentration time curve from zero to infinity (AUCinf) of QRL-201 | Predose up to 24 hours post dose | Endpoints: PK: AUC (0-inf) of QRL-201 |
| Pharmacokinetics (plasma): Time of maximum concentration (Tmax) of QRL-201 | Predose up to 24 hours postdose | Endpoints: PK: Tmax of QRL-201 |
Countries
Belgium, Canada, Germany, Ireland, Netherlands, United Kingdom
Contacts
STUDY_DIRECTORManoj Malhotra, MD
QurAlis Corporation
Outcome results
None listed